Background/Aims Functional lumen imaging probe (FLIP) Panometry has demonstrated utility in the assessment of esophageal motility as a complement to existing methodologies like high-resolution manometry. However, as FLIP is typically performed with sedation during routine endoscopy, there is potential for impact of sedation agents on esophageal motility. We aim to examine the effects of conscious sedation with midazolam and fentanyl on FLIP Panometry metrics and classification. Methods A cross-over study was conducted on 12 healthy, asymptomatic volunteers that completed FLIP while sedated with intravenous fentanyl and midazolam and while awake on a separate day. FLIP was performed in the same manner in both conditions with transoral placement of the FLIP and stepwise FLIP filling. During awake FLIP, subjects also rated the presence and intensity of esophageal perception. Results In both experimental conditions, all subjects demonstrated normal motility. The esophagogastric junction distensibility index was lower (median [interquartile range]: 5.8 [5.15-6.85] vs 8.9 [7.68-9.38] mm2/mmHg; P = 0.025), and the FLIP pressure was higher (46.5 [38.125-52.5] vs 33 [26-36.8] mmHg; P = 0.010) in the sedated condition compared to the awake condition. Maximum esophagogastric junction diameter and body distensibility plateau were no different between conditions (P = 0.999 and P = 0.098, respectively). Perception of esophageal sensation during awake FLIP was reported in 7/12 (58%) subjects. Conclusions While numeric differences in FLIP Panometry metrics were observed between sedated and awake FLIP in healthy subjects, these differences did not change the FLIP Panometry diagnosis. Sedated FLIP offers a well-tolerated method to assess esophageal motility during endoscopy. [ABSTRACT FROM AUTHOR]